We propose to determine red cell life span simultaneously using 51 Cr and indogenous CO production in additional sickle cell disease individuals. We will continue to study CO production in sickle cell patients in and out of mild pain crisis. We propose to determine the effect of graded exercise on endogenous CO production in healthy individuals with sickle cell trait. To examine the possibility that Fetal hemoglobin containing cells (F-cells) in sickle cell disease may be monoclonal, we propose to use G-6-PD isoenzymes as markers in women with sickle cell disease who are doubly heterozygous for electrophoretrically distinct G-6-PD isoenzymes. We are studying the application of differential hemolysis method (Blood 47:883, 1976) for enrichment of F-cells in these patients. In a preliminary study of the leucocytosis in adult SS patients with absent spleen function, the pattern of total and differential leucocyte counts in SS patients was found to be quite similar to that of individuals splenectomized for non-hematologic reasons. We plan to extend the observations by comparing the granulocyte reserve and marginating pools in these two groups using prednisone and epinephrine to define the role of absent spleen in the leucocytosis of SS. The undersigned agrees to accept the responsibility for the scientific and technical conduct of the project and for provision of required progress reports if a grant is awarded as a result of this application.